Diseases such as diabetes mellitus (DM), occur at the cellular level and are inflicted by insufficient energy required to continuously maintain the structure and function of cells, particularly in the pancreas. All cells with depleting energy supplies are less capable of their genetically programmed performances, and in this case defective insulin capabilities. Cellular respiration is the process for the enzymatic breakdown of glucose in the presence of oxygen to produce cellular energy in the form of ATP. It occurs in three steps: Glyoclyis, the Citric Acid Cycle (CAC), and the Electron Transport System. In glycolysis, each molecule of glucose is converted to two molecules of pyruvic acid and a net yield of 2 NADH. The pyruvic acid then diffuses into the inner compartment of the mitochondrion where a transition reaction occurs to prepare the pyruvic acid for entry into the next stage of respiration, the CAC. In the transition reaction, pyruvate is converted into acetyl and then carried into the CAC by coenzyme A (CoA). The CAC occurs in the inner mitochondrial matrix and results in a net yield of 2 ATP per 2 acetyl CoA. In addition, a net yield of 6 NADH and 2 FADH2 is also accomplished. In the last step of cellular respiration, the electron transport system, a series of enzymes on the inner mitochondrial membrane receive electrons released from the NADH and FADH2 produced during the CAC and glycolysis. However, the NADH produced during glycolysis must first be transported across the inner mitochondrial membrane to enter the electron transport chain. The mechanism for transporting the NADH produced during glycolysis across the inner mitochondrial membrane is the malate-aspartate shuttle. The malate-aspartate shuttle transports an oxidized version of the NADH, NAD+, across the inner mitochondrial membrane. Once across, the NAD+ is reduced to NADH and is now free to transfer its high energy electrons to the electron transport chain. In the electron transport chain, as the electrons are passed along the series of enzymes on the inner mitochondrial membrane, the electrons release energy to power a process called chemiosmosis by which H+ ions are actively transported across the inner mitochondrial membrane into the outer mitochondrial compartment. The H+ ions then travel back through special pores in the membrane, which is believed to fuel the process of ATP synthesis. A net yield of 34 ATP is generated per glucose molecule during the electron transport system.
Cells in a person suffering from diabetes are unable to properly perform cellular respiration. As a result, these cells are unable to fully harvest the available glucose and therefore are unable to produce as much energy as the cells of a non-diabetic person. Further compounding this cellular malfunction we know the receptor sites, i.e., glucose transporters (Glut4) are also down regulated. Now, the increasing glucose enables toxic oxidation and inflammatory compounds to further impair cellular function at the cytosolic and nuclear levels; this creates a need for repair or replacement of these cells. Energy required via the citric acid cycle (CAC) is critically required at this point lest we have further reduction of the vesicle associated membrane protein (VAMP) and diminishing mitochondrial numbers. In man, a cell functions alone or in composite utilizing all its energy for these genomic processes. If the cell requires repair, the primary function of the cell is diminished with repair requiring a portion of the cell's total energy. If the repair is significant, all cross talk and synchronization of cell networking is diminished and cell function may stop until repair is effected unless gene silencing or apoptosis intervenes.
From this point forward the use of methyl pyruvate (MP), ethyl pyruvate (EP) and their manifold alkyl analogues (bimethylated and ethylated composites and methyl-ethyl composites of pyruvate) solely or in any and all combinations will be represented by MP as their template for the energy and anti-inflammation needed to resolve the above scenario. Additionally, HbA1c is a protein of hemoglobin in the red blood cells (RBC) that irreversibly attaches to plasma glucose for the three-month life span of the RBC. The percent of HbA1c correlates with blood glucose levels that measure: normals from four (4%) percent to six (6%) percent and diabetics at ≧six (6%) percent. The mathematical correlation between blood glucose and glycohemoglobin (HbA1c) is demonstrated in the graphic depiction of FIG. 1 (The conversion factor of MPG to mg/dl of glucose, is 18 times MPG).
Methyl pyruvate performs as a lipophilic antisense-like bullet that penetrates cell membranes, mitochondrial membranes and nuclear membranes with its active and passive delivery of energy via protons, adenosine triphosphate manufacture (ATP) and methylation. This energy delivering metabolic bullet upregulates all cytosolic and nuclear capabilities. It can even negate messenger RNA (mRNA) expression. Now, because of instant protons and pyruvate delivered, there is immediately empowered glycolysis and/or CAC production of ATP and the cell functions with more efficient performance. Through this newly available energy, gene silencing can be reversed, repairs completed, apoptosis performed, and the cell is upgraded and/or divides (cell partitioning) into a new and improved cell having shed its prior oxidative cellular/genetic debris. In DM this means improved Glut4 networking, improved insulin sensitivity, increased intra and intercellular networking and increased superoxide dismutase (SOD) production. Further, due to MP, many nutrients and complicit molecules including peroxisome proliferator-activator receptor (Ppars) will now function more effectively and efficiently, i.e. as infused and increased cellular energy can now affect niacinamide (B3) and nicotinamide adenine dinucleotide (NAD) at an intracellular level that enables and protects beta cell function. In addition, energy reduces the level of HbA1c, increases cell life span and prepares FOXO3a to stop proteolysis initiation, and/or initiate apoptosis when and where appropriate in the cell cycle. Methylation ability afforded by MP assists in cellular methylation but can also afford to enhance gene expression as it retracts the histone sheath of the chromatin allowing increased genetic expression. With all vitamins, all amino acids, all nutrients, hydronium ion and water transport, all cation and anion channel functions, lipid metabolism, protein metabolism, glucose metabolism, organ functioning, genomic protection replication and functioning, MP enables all of these individual physiologic roles and applications. (Ethyl and Methyl pyruvates have been tested in human volunteers and have been shown to be safe in clinically prescribed doses.)
The failing of glucose-insulin networking in T2DM creates a toxic environment whereby ROS, especially unutilized glucose, causes a down regulation of energy production. The down regulation of energy production causes mitochondrial energy production to wane which leads to the diminishing of all cell/organ function.
By the above process, aging progresses and a certain level of energy depletion disease manifests that relates to the cells inability to function. The energy that is manufactured is now utilized for cell/organ repair. Finally, due to the lack of energy, gene silencing and/or apoptosis occurs. In some cases, P53 and P21 compromise occurs which allows cancer to emerge.
Supplying the present invention's ex vivo energy to the above scenario causes the energy-lack disease process to cease. In particular, energy repletion enables rejuvenation and healing that restores cell/organ function. The present invention's ex vivo energy delivers protons and methylation, and then pyruvate to the CAC cycle as a secondary energy source that is harnessed without the energy depleting preparation.
Neuropathy, diabetic as example, relates to the pathology caused by glycosylation, ROS and damage to neurons, Glut 4 down regulation, associated vascular deterioration, nutritional depletion and finally no energy to correct any/all of the above. The present invention's ex vivo energy provides a superimposed energy source for healing and restoration which can reverse neuropathology.
The same ex vivo energy source, if you reverse engineer most diseases, appears to be the first domino that requires fixing (energizing) to slow and reverse the pathology. This template would apply to Parkinson's disease, ALS, Alzheimer's disease, CVD, CA, dementia, neurodegenerative disease, organ failure, T2DM and stem cell/organ transplant survival. Energy transplantation by the present invention's ex vivo energy up regulates transcription, translation, endoplasmic reticulum and ribosomal functioning, PARP, P53 and P21 and mitochondrial and nuclear functioning. Accordingly, the use of the present invention's ex vivo energy is designed to provide an innovative energy source for the curing of diseases that are triggered by a depletion in the energy level of the cells.